This invention relates to a stent used for dilating a stenotic lesion of a blood vessel.
PTCA (percutaneous transluminal coronary angioplasty) is a widely adopted treatment in the case of coronary artery stenotic diseases such as stenocardia and myocardial infarction. In PTCA, the stenotic lesion of the blood vessel (coronary artery) is pushed open from its inside to enable the blood to flow therethrough.
In order to avoid restenosis of the blood vessel after the blood vessel dilatation, an expandable intraluminal graft ("stent") as disclosed in U.S. Pat. No. 4,733,665 has been developed.
A stent is a cylindrical medical device used to maintain the inside opening of a body duct such as a blood vessel and bile duct. The stent is introduced into the body duct in compacted or folded thin state. When the stent is positioned in the target site (stenosis lesion), the stent is expanded and pressed into place against the inner wall of the lumen and stands there to serve a structural support for the lumen.
There are two mechanisms for the stent expansion. One is the mechanism wherein the stent is pushed radial-outwardly from its inside by a n external force, namely, by placing a balloon inside the stent and inflating the balloon. The other is the mechanism wherein a stent capable of restoring its original shape is folded in a compact shape, and the force retaining such compact shape is removed to allow for the stent to self-expand in radially outward direction by its own restorative force.
The stent of the first type which is expanded in radially outward direction by the external force of the inflated. balloon is called a balloon-expanded stent, and the stent of this type is not self-expandable. The balloon-expanded stent is made of a metal material which is less likely to restore its original shape once the stent is expanded, and in view of biological safety, the preferred materials are inactive in a body such as stainless steel, tantalum, and the like.
The stent that expands by its own restorative force is called a self-expandable stent, and the stent of this type is provided with a constriction means and is selfexpandable. For example, the stent may be constricted and accommodated in a tube having an outer diameter smaller than the inner diameter of the target lesion, and once the distal end of the tube has reached the target lesion, the stent may be pushed out of the tube to allow its self-expansion. As described above, the self-expandable stent should be capable of restoring its original shape, and therefore, such stent is made from stainless steel, a superelastic alloy, or a shape memory alloy (nickel-titanium alloy, in the latter two cases).
Of the self-expandable stents, the one employing a super-elastic alloy (shape memory alloy) is disclosed in JP-B-5-43392.
As described above, most of currently available stents are made of a metal. A metal has been selected in view of its inherent physical properties and particular function as well as safety and compatibility with the tissue. A metal, however, is an utterly foreign matter from the standpoint of blood, and the blood induces thrombus formation and platelet activation to induce vascular smooth muscle cell (VSMC) migration and proliferation.
Since the stent generally has a complex net structure, the placement is always involved with some risk of narrowing or blockage of the blood vessel by thrombus formation or vascular smooth muscle cell migration and proliferation, and this is the reason why the patient is administered with an antithrombotic agent such as heparin or warfarin for approximately two weeks following the stent placement until the inner surface of the stent is substantially covered with hemangioendothelial cells. Such administration of the antithrombotic agent may result in the occurrence of a bleeding complication from the artery at the puncture site or from the peripherals.
If the restenosis short after the stent placement induced by the vascular smooth muscle cell migration and proliferation through the platelet activation could be avoided, and dosage and period of the antithrombotic administration could be reduced or nulled, the results should be shorter lengths of hospital stay and decreased bleeding complications.
In the meanwhile, various methods have been developed for the purpose of rendering medical devices antithrombogenic.
U.S. Pat. No. 3,810,781 discloses a method for imparting antithrombogenicity with a surface of plastic resin wherein a cationic surfactant is adsorbed on the plastic surface, and heparin which has been crosslinked with glutaraldehyde is ionically bonded to the surfactant.
U.S. Pat. No. 4,118,485 discloses a method for imparting antithrombogenicity with a surface of substrate of a plastic resin, glass, or metal wherein the substrate surface is coated with a heparin-quaternary amine complex compound, and the surface is further treated with glutaraldehyde to form a Schiff base to thereby impart antithrombogenicity with the substrate surface. There is also disclosed a method wherein the substrate surface is coated with a heparin-quaternary amine (benzalkonium chloride) complex compound to impart antithrornbogenicity with the substrate surface.
In these methods, however, the heparin, the heparin-quaternary amine compound, or the heparin-quaternary amine-glutaraldehyde compound is attached to the substrate surface through IPN (interpenetrating network) structure or intermolecular force, and therefore, the heparin-substrate bond is not sufficiently strong as in the case of covalent bond.
EP-A-679373 discloses a method wherein the stent is imparted with antithrombogenicity by vacuum depositing a Parylene resin coating on the stent.
JP-B-6-38851 discloses various methods for covalently bonding heparin or a derivative thereof to the surface of various plastic resin materials. In these methods, the heparin derivative is covalently bonded to the substrate surface, and the heparin derivative is unlikely to be removed from the surface. However, in the case of metal material which is less active than the plastic material, it is unknown whether such heparin derivative can be covalently bonde d to the metal surface by the same procedure. Even if such heparin derivative could be covalently bonded to the metal surface of a stent, it is still unknown whether the heparin derivative can effectively suppress the vascular smooth muscle cell migration and proliferation.
Stainless steel, the most widely adopted material for a stent, is radiotranslucent, and since a stent has a net structure, and the width of the stainless steel item which constitutes a net has a thickness of 0.2 mm, it has been quite difficult to confirm the exact location and the geometry of the radiotranslucent stainless steel stent during and after the surgery. A radiopaque marker has been provided on the catheter to indicate the location of the stent. Such radiopaque markers on the catheter, however, have been far from being satisfactory since there is a considerable risk of the stent becoming displaced from the predetermined site on the catheter. In addition, incapability of direct confirmation of the catheter geometry often resulted in the failure of finding the event of insufficient stent expansion and "elastic recoiling" which is the recovery of the once expanded stent to its initial unexpanded state by the restoration tendency to some extent inherent to all metal materials.
In order to obviate such situation, EP-A-679372 discloses a stent provided with a radiopaque marker. A stent plated with a metal for the purpose of imparting radiopacity, however, suffers from the risk of inducing the narrowing and blocking of the b lood vessel at the site where it is placed.